The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of a diminished frequency of proliferating cells to parasite antigen and of the production of the antiproliferative cytokines, IL-10 and TGF-beta. Filter immunoplaque assays for the major cytokines have been developed and used to demonstrate that in helminth infections of humans there is an expansion of Th2 CD4+ cells, the phenotypes of which are currently being delineated. In vitro models of parasite-antigen driven antibody production along with recombinant cytokines and neutralizing antibodies to them have been used to understand the signals necessary to regulate antibody production in response to parasite antigen.